Nucleocytoplasmic Shuttling of Cytoskeletal Proteins: Molecular Mechanism and Biological Significance
Figure 1
Regulatory mechanisms of cytoskeletal proteins in the nucleus. (a) Possible molecular mechanisms of the nuclear shuttling of actinin-4, actin, and Arp4 through the NPC. Actinin-4 and actin are predominantly localized to the cytoskeleton whereas Arp4 is a nuclear-specific actin homologue. In addition to the bidirectional passage by passive diffusion or spontaneous transport, actinin-4 and actin are actively exported by karyopherins, leading to their predominant localization in the cytoplasm. Arp4 does not contain functional NLS or NES in its amino acid sequence, suggesting that passive diffusion is a driving force for the nuclear transport of this molecule. It may be possible that their transport through the NPC is effected by unknown karyopherins or their binding partners, especially in the case that they possess signal sequences such as NLS or NES. (b) Three possible steps regulating the nuclear localization of cytoskeletal proteins. The balance of nucleocytoplasmic distribution can be altered by (1) a change in the amount of NPC-accessible molecules in the cytoplasm, (2) transport through the NPC, which is regulated by the combination of passive diffusion, active transport, and karyopherin-independent spontaneous transport, and (3) retention in the nucleus.
